The need for complexity in microfluidic systems is increasing rapidly as sophisticated functions—chemical reactions and analyses, bioassays, high-throughput screens, and sensors—are being integrated into single microfluidic devices. Complex systems of channels require more complex connectivity than can be generated in conventional two-dimensional microfluidic systems having a single level of channels, since such typical single-level designs do not allow two channels to cross without fluidically connecting. Most methods for fabricating microfluidic channels are based on photolithographic procedures, and yield such two-dimensional systems. There are a number of more specialized procedures, such as stereolithography (see for example, K. Ikuta, K. Hirowatari, T. Ogata, Proc. IEEE MEMS '94, Oiso, Japan, Jan. 25-28, 1994, pp. 1-6), laser-chemical three-dimensional writing (see for example, T. M. Bloomstein, D. J. Ehrlich, J. Vac. Sci. Technol. B, Vol. 10, pp. 2671-2674, 1992), and modular assembly (see for example, C. Gonzalez, R. L. Smith, D. G. Howitt, S. D. Collins, Sens. Actuators A, Vol. 66, pp. 315-332, 1998), that yield three-dimensional structures, but these methods are typically time consuming, difficult to perform, and expensive, and are thus not well suited for either prototyping or manufacturing, and are also not capable of making certain types of structures. Better methods for generating complex three-dimensional microfluidic systems are needed to accelerate the development of microfluidic technology. The present invention, in some embodiments, provides such improved methods for generating complex three-dimensional microfluidic systems.
It is known to use a stamp or mold to transfer patterns to a surface of a substrate (see for example, R. S. Kane, S. Takayama, E. Ostuni, D. E. Ingber, G. M. Whitesides, Biomaterials, Vol. 20, pp. 2363-2376, 1999; and Y. Xia, G. M. Whitesides, Angew. Chem. Int. Ed. Engl., Vol. 37, pp. 551-575, 1998; U.S. Pat. No. 5,512,131; International Pat. Publication No. WO 97/33737, published Sep. 18, 1997). Most conventional soft lithographic techniques, for example, microcontact printing (μCP) (see for example, C. S. Chen, M. Mrksich, S. Huang, G. M. Whitesides, D. E. Ingber, Science, Vol. 276, pp. 1425-1428, 1997; A. Bernard, E. Delamarche, H. Schmid, B. Michel, H. R. Bosshard, H. Biebuyck, Langmuir, Vol. 14, pp. 2225-2229, 1998) and micromolding in capillaries (MIMIC) (see for example, N. L. Jeon, I. S. Choi, B. Xu, G. M. Whitesides, Adv. Mat., Vol. 11, pp. 946-949, 1999; E. Delamarche, A. Bernard, H. Schmid, B Michel, H. Biebuyck, Science, Vol. 276, pp. 779-781, 1997; E. Delamarche, A. Bernard, H. Schmid, A. Bietsch, B. Michel, h. Biebuyck, J. Am. Chem. Soc., Vol. 120, pp. 500-508, 1998; A. Folch, A. Ayon, O. Hurtado, M. A. Schmidt, M. Toner, J. Biomech. Eng., Vol. 121, pp. 28-34, 1999; A. Folch, M. Toner, Biotech. Prog., Vol. 14, pp. 388-392, 1998), have been limited to procedures that pattern one substance at a time, or to relatively simple, continuous patterns. These constraints are both topological and practical. The surface of a stamp in μCP, or of a channel system in MIMIC, is effectively a two-dimensional structure. In μCP, this two-dimensionality of the stamp limits the types of patterns that can be transferred to those comprising a single “color” of ink in the absence of a way of selectively “inking” different regions of the stamp with different materials. Patterning of multiple “inks” using conventional methods requires multiple steps of registration and stamping. In MIMIC, the two-dimensional channel system limits patterning to relatively simple, continuous structures or requires multiple patterning steps.
There remains a general need in the art for improved methods for forming patterns on surfaces with soft lithographic techniques, and for providing techniques able to pattern onto a surface arbitrary two-dimensional patterns and able to form complex patterns comprised of multiple regions, where different regions of the pattern can comprise different materials, on a surface without the need for multiple steps of registration or stamping and without the need to selectively “ink” different regions of the stamp with different materials. The present invention, in some embodiments, provides such improved methods for forming patterns on surfaces with soft lithographic techniques.